Prostate cancer is the second most common cancer in men after skin cancer and the second leading cause of cancer death in men after lung cancer. The risk of developing prostate cancer increases with age. It is more common in African Americans. In early stages, prostate cancer generally causes no symptoms and is typically detected by screening. The preferred diagnostic procedures are digital rectal examination (DRE), PSA testing, and ultrasound-guided transrectal prostate biopsy. Bone metastases are common in advanced prostate cancer and can be diagnosed using a bone scan. Because most patients with prostate cancer are of advanced age, life expectancy and the histological evaluation of a tumor biopsy should be taken into account when planning treatment. Radical prostatectomy and radiotherapy are indicated in young patients. In older patients, “watchful waiting” (i.e., purely symptomatic treatment) and “active surveillance” (i.e., continuous restaging and initiation of curative measures if tumor progresses) are also a treatment option since localized prostate cancer typically has a slower growth rate and a better prognosis compared to other malignancies.
- Incidence: following skin cancer (i.e., melanoma and nonmelanoma combined) most common cancer in men in the US 
- Mortality: in 2020, second leading cause of cancer deaths in men in the US (after lung cancer)
Epidemiological data refers to the US, unless otherwise specified.
Risk factors 
- Advanced age (> 50 years) 
- Family history
- African-American descent
- Genetic disposition (e.g., BRCA2, Lynch syndrome)
- Most common type: adenocarcinoma expressing PSA 
- Most common localization: peripheral zone (posterior lobe) of prostate 
Prostate cancer is commonly localized in the Peripheral zone (Posterior lobe).
Early-stage prostate cancer
- Typically asymptomatic
Advanced-stage prostate cancer
- Loss of appetite
- Weight loss
Urinary symptoms 
- Urinary retention
- Hydronephrosis (associated with flank pain and renal failure)
- Bone pain (due to bone metastasis, especially in the lumbosacral spine)
- Neurological deficits (due to spinal cord compression)
Lymphedema (caused by obstructing metastases in the lymph nodes) leading to:
- : characterized by a homogenous, rubbery, and nontender prostate
- : extremely painful, swollen, and tender prostate
- Other tumors (e.g., lymphoma or metastasis)
The differential diagnoses listed here are not exhaustive.
Approach to suspected prostate cancer
- Physical examination, including digital rectal examination (DRE)
- Measurement of prostate-specific antigen (PSA) levels
- In case of suspicious findings/elevated PSA levels: multiple transrectal, ultrasound-guided biopsies to confirm the diagnosis.
- Staging in case of confirmed prostate cancer to assess disease extent and plan adequate treatment.
Screening and basic diagnostics 
- Low sensitivity (approx. 30%)
- Good specificity (approx. 90%) : Irregular and nodular prostate is suspicious for malignancy, but not specific for cancer.
Physiological DRE findings
- Roughly heart-shaped
Early stage prostate cancer DRE findings
- Localized indurated nodules
- Otherwise smooth
Advanced stage prostate cancer DRE findings
- Asymmetric areas
- Frank nodules
Prostate-specific antigen (PSA) levels
Other blood tests
- Technique: ∼ 12 prostate samples are taken from different areas of the prostate guided by transrectal ultrasonography (TRUS) under local anesthesia and prophylactic antibiotics.
Interpretation: : When prostate cancer is present in the biopsy, the tumor is graded using the Gleason score.
- Calculated based on the microscopic appearance of prostate cancer
- Higher score indicates a worse prognosis (ranges from 2 to 10)
- Score is established by adding the Gleason grades of the most prevalent and the second most prevalent differentiation pattern within the biopsy
- Grade ranges from 1 to 5
- Grade 1: well-differentiated, microscopically uniform glands without invasion into adjacent healthy prostate tissue
- Grade 5: undifferentiated cancer cells with no glandular differentiation
- In confirmed prostate cancer to assess the extent of the disease
- Should be performed, if advanced cancer is suspected by either PSA levels > 10 ng/mL or a Gleason score ≥ 7
- Regional metastasis: pelvic lymph nodes
Distant metastasis: most commonly bone metastases (less common: lungs, liver, and adrenal glands)
- Prostate cancer spreads to the bones early.
- Spinal metastasis are common and occur because of spread through the Batson vertebral venous system.
- Metastases from prostate cancer are predominantly osteoblastic. Also, osteolytic metastases can be found, causing pathologic fractures.
- Occult prostate cancer: prostate cancer that is not detected by symptoms caused by the primary cancer but by cancer metastasis (e.g., back pain caused by bone metastases)
Complications following surgery or radiotherapy
We list the most important complications. The selection is not exhaustive.
- The treatment plan is based upon:
- Patient's age
- Life expectancy
- Medical condition
- Results of imaging studies, PSA levels, and the Gleason score are taken into consideration when evaluating the different treatment options.
Management of localized disease
Active surveillance 
- Regular follow-ups with cancer restaging instead of treatment
- Preferred option for most early-stage cancers)
- Treatment is only started if the tumor progresses.
Watchful waiting 
- Less intensive type of follow-up than active surveillance
Best approach in a number of different cases, including:
- Elderly patients with slow-growing tumors
- Life-limiting comorbidity
- Life expectancy < 10 years due to other causes
- Systemic or local treatment to relieve symptoms is initiated if symptomatic progression of the tumor occurs.
Radiation therapy 
- Indication: localized disease
Radical prostatectomy 
- Indication: localized disease
- Variant: salvage prostatectomy 
Antiandrogen therapy 
- Indication: androgen sensitive localized high-grade or metastatic prostate cancer
Medical castration: gonadotropin-releasing hormone (GnRH) agonists (e.g., leuprolide) or antagonist (e.g., degarelix)
- May be combined with an antiandrogen (e.g., flutamide, bicalutamide) for complete androgen blockade.
- Androgen synthesis inhibitor
- Inhibition of CYP17 gene products (including 17α-hydroxylase and 17,20-lyase) → block of androgen synthesis in the adrenal glands, testis, and tumor tissue
- Combined with glucocorticoids to avoid adrenal insufficiency
- Adverse effects include; UTIs, cardiac complications (e.g., arrhythmia, hypertension; , atrial fibrillation), hypokalemia (via increase of mineralocorticoids)
- Continuous administration of GnRH receptor agonists causes a transient increase in androgen levels during the first few weeks of therapy, followed by a sustained decrease.
- Surgical castration
- Medical castration: gonadotropin-releasing hormone (GnRH) agonists (e.g., leuprolide) or antagonist (e.g., degarelix)
Management of disseminated disease
- Chemotherapy with docetaxel
- Osteoclast inhibitors (e.g., bisphosphonates, denosumab) in bone metastases
Management of castration-resistant prostate cancer (CRPC)
- Overview: CRPC is characterized by disease progression (elevated serum PSA levels, progression of pre-existing metastasis, or new metastases) despite ADT (surgical or medical castration).
- General approach
- CRPC with asymptomatic bone metastases
- CRPC with symptomatic bone metastases